2011 Grants - Suo

Fighting Against Alzheimer's Selective Cholinergic Neurodegeneration

2011 Novel Pharmacological Strategies to Prevent Alzheimer's Disease

In the brains of persons with Alzheimer's disease, a class of nerve cells known as basal forebrain cholinergic neurons are selectively vulnerable to cell death, especially in the early stages of disease. The explanation for this selective vulnerability is unclear, and current animal models of Alzheimer's disease do not replicate the vulnerability seen in the human brain.

William Z. Suo, M.D. and colleagues have developed a new strain of mice that exhibit Alzheimer's-like pathology in the brain, including selective vulnerability of the basal forebrain cholinergic neurons. Furthermore, by studying nerve cells in culture, the researchers have found preliminary evidence that this vulnerability can be prevented by inhibiting a receptor known as the muscarinic 2 (M2) receptor.

imer's disease. The researchers will determine ideal doses of a selective M2 inhibitor, and then determine its effects on preserving forebrain cholinergic neurons and cognitive function. These studies may pave the way for development of new treatment options to prevent or slow neurodegeneration in Alzheimer's disease.